Induction of a selective and persistent extravasation of neutrophils into the peritoneal cavity by tryptase mouse mast cell protease 6.
Recombinant mouse mast cell protease 6 (mMCP-6) was generated to study the role of this tryptase in inflammatory reactions. Seven to forty-eight hours after the i.p. injection of recombinant mMCP-6 into BALB/c, mast cell-deficient WCB6F1-Sl/Sl(d), C5-deficient, or mMCP-5-null mice, the number of neutrophils in the peritoneal cavity of each animal increased significantly by >50-fold. The failure of the closely related recombinant tryptase mMCP-7 to induce a comparable peritonitis indicates that the substrate specificities of the two tryptases are very different. Unlike most forms of acute inflammation, the mMCP-6-mediated peritonitis was relatively long lasting and neutrophil specific. Mouse MCP-6 did not induce neutrophil chemotaxis directly in an in vitro assay, but did promote chemotaxis of the leukocyte in the presence of endothelial cells. Mouse MCP-6 did not induce cultured human endothelial cells to express TNF-alpha, RANTES, IL-1alpha, or IL-6. However, the tryptase induced endothelial cells to express large amounts of IL-8 continually over a 40-h period. Neither enzymatically active mMCP-7 nor enzymatically inactive pro-mMCP-6 was able to induce endothelial cells to increase their expression of IL-8. Although the mechanism by which mMCP-6 induces neutrophil accumulation in tissues remains to be determined, the finding that mMCP-6 induces cultured human endothelial cells to selectively release large amounts of IL-8 raises the possibility that this tryptase regulates the steady state levels of neutrophil-specific chemokines in vivo during mast cell-mediated inflammatory events.
Huang
C
C
Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA 02115, USA.
Friend
D S
DS
Qiu
W T
WT
Wong
G W
GW
Morales
G
G
Hunt
J
J
Stevens
R L
RL
D000818:Animals; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology*; D053818:Chymases; D016207:Cytokines / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism; D004765:Enteropeptidase / Q000235:genetics; D004792:Enzyme Precursors / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology*; D010538:Peritonitis / Q000201:enzymology / Q000209:etiology / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018411:Spodoptera; D053802:Tryptases
D018925:Chemokines; D016207:Cytokines; D004792:Enzyme Precursors; D011993:Recombinant Fusion Proteins; C509190:Tpsb2 protein, mouse; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; C509222:Tpsab1 protein, mouse; D053802:Tryptases; D004765:Enteropeptidase